We will develop new methods of cell-cycle analysis and apply them to a variety of experimental systems in an effort to better understand the malignant process and to optimize the treatment of cancer by chemotherapy and radiotherapy. l. The fraction of labeled mitoses (FLM) method will be pursued, including the provision of a service for computer analysis of FLM data, sensitivity testing of the method, and the compilation and interpretation of FLM results.2. Experiments will be continued on the mechanism of arrest of nonproliferating cells using cytophotometry, autoradiography, and premature chromosome condensation. 3. Flow systems (flow microfluorimetry and multiparametric cell sorting) will be adapted and applied to cell-cycle analysis, including: a. Extraction of the fraction of cells in G1,S,G2 and M using computer analysis of histograms of cellular DNA content as measured by flow microfluorimetry. b. Modeling, new methods of analysis, and cell culture and animal experiments of progression and dispersion of synchronous cells as seen in the DNA histogram. c. The development of practical alternatives to conventional FLM analysis by using liquid scintillation detection of cells sorted on the basis of DNA content, light scatter and cytochemical markers. d. Cytochemistry and morphology of sorted cells to define markers for cell-cycle stage, DNA synthesis, and nonproliferation.